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A step toward the $1,000 personal genome using readily available lab equipment

The theoretical price of having one's personal genome sequenced just fell from the prohibitive $20 million dollars to about $2.2 million, and the goal is to reduce the amount further--to about $1,000--to make individualized prevention and treatment realistic.

The sharp drop is due to a new DNA sequencing technology developed by Harvard Medical School (HMS) researchers Jay Shendure, Gregory Porreca, George Church, and their colleagues, reported on August 4 in the online edition of Science. The team sequenced the E. coli bacterial genome at a fraction of the cost of conventional sequencing using off-the-shelf instruments and chemical reagents. Their technology appears to be even more accurate and less costly than a commercial DNA decoding technology reported earlier this week.

The Church group's technology is based on converting a widely available and relatively inexpensive microscope with a digital camera for use in a rapid automated sequencing process that does not involve the much slower electrophoresis, a mainstay of the conventional Sanger sequencing method.

"Meeting the challenge of the $1,000 human genome requires a significant paradigm shift in our underlying approach to the DNA polymer," write the Harvard scientists.

The new technique calls for replicating thousands of DNA fragments attached to one-micron beads, allowing for high signal density in a small area that is still large enough to be resolved through inexpensive optics. One of four fluorescent dyes corresponding to the four DNA bases binds at a specific location on the genetic sequence, depending on which DNA base is present. The fragment then shines with one of the four colors, revealing the identity of the base. Recording the color data from multiple passes over the same sequences, a camera documents the results and routes them to computers that reinterpret the data as a linear sequence of base pairs.

In their study, the researchers matched the sequence inform ation against a reference genome, finding genetic variation in the bacterial DNA that had evolved in the lab.

"These developments give the feeling that improvements are coming very quickly," said HMS professor of genetics Church, who also heads the Lipper Center for Computational Genetics, MIT-Harvard DOE Genomes to Life Center, and the National Institutes of Health (NIH) Center for Excellence in Genomic Science.

"The cost of $1,000 for a human genome should allow prioritization of detailed diagnostics and therapeutics, as is already happening with cancer," Church said.

The Church lab is a member of the genome sequencing technology development project of the NIH-National Human Genome Research Institute.


Source:Harvard Medical School

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